Halopropargyl aryl ether compounds



2 I HALOPROPARGYL ARYL ETHER COMPOUNDS Shigeo Seki, Bunzo Nomiya, and Hiroshi Ogawa, Tokyo,

Japan, assignors to Meiji Seika Kaisha, Ltd., Tokyo, Japan, a corporation of Japan No Drawing. Fiied June 6, 1963, Ser. No. 285,871 Claims priority, application Japan, June 30, 1962, 37/26,896; Mar. '7, 1963, 38/10,431 13 Claims. (Cl. 260-465) This invention relates to new halopropargyl aryl ether compounds and to processes for the production of the same compounds.

The new compounds halopropargyl aryl ethers according to this invention maybe represented by the following general formula wherein Ar stands for an aryl group, particularly phenyl and naphthyl groups, which bears on the aromatic nucleus at least one of the substituents selected from the group consisting of halogen, alkyl, alkoxy, alkynyloxy, phenyl, aoyl, acylamino, carboxyl, carboalkoxy, carbarnoyl, nitro and cyano radicals; R and R may be the same or different and stand for a member selected from the group consisting of hydrogen, alkyl and phenyl groups; and X stands for ahalogen atom selected from the group consisting of bromine, iodine and chlorine. These new compounds according to the present invention have not been reported in any publication, but we have now found that these halopropargyl aryl ether compounds show an activity inhibitory to the growth of eumycetes and are particularly useful for the control or treatment of Water-eczema.

This invention also includes a process for the production of these new halopropargyl aryl ether compounds which comprises reacting a proper halogenation agent in a proper manner with the corresponding propargyl aryl ether compound of the general formula have the same significances as 45 wherein Ar, R and R 3,322,8l3 Patented May 30, 1967 The corresponding propargyl aryl ether compound used as the starting material in the process of the invention may be readily prepared by reacting a proper propargyl halide in a proper solvent such as alcohol with an alkali metal salt of phenol or naphthol which bears the corresponding substituent or substituents on the aromatic nucleus.

As the halogenation methods which may be employed in the process of the invention, there are mentioned conventional methods of halogenation which are able to convert an acetylene compound into the corresponding acetylene halide. For instance, there may be applied Adolf Baeyers method according to which an acetylene compound is added to an aqueous suspension of cuprous hydroxide and the resulting cuprous aoetylide is reacted with a halogen to give the acetylene halide compound (refer to Ber., 18, 2284 1855)) method of Straus, F., et 211., according to which an acetylene compound is reacted with a salt of hypo-halogenous acid to give the acetylene halide compound (refer to Ber. 63, 1868 (1930)); and I. U. Nefs method according to which an acetylene compound is reacted with a halogen and the resulting dihalogen compound is reacted with an alkali metal to give the acetylene halide compound (refer to Ann, 308, 325 (1899)). In case the halogenation agent is chlorine gas, the process of the invention may be easily carried out by reacting chlorine gas with a starting propargyl aryl ether compound in a proper solvent such as methanol, ethanol and water at a temperature of 20 C. to +40 C., preferably +5 C. to +15 C. and in the presence of an alkali metal hydroxide such as sodium and potassium hydroxides.

Among the particularly useful products which can be obtained by the process of the present invention, there may be mentioned e.g. 4*bromophenyl iodopropargyl ether, 2,6 -dichlorophenyl iodopropargyl ether, 2,4,5-trichlorophenyl iodopropargyl ether, 4-bromophenyl chloropropargyl ether, 2,4 dichlorophenyl chloropropargyl ether and 2,4,5-trichlorophenyl chloropropargyl ether.

In order to demonstrate the anti-microorganism activity of the halopropargyl aryl ether compounds of the invention, the minimum concentration of some compounds inhibitory to the growth of various microorganisms are determined by the serial dilution method. The results obtained are shown in Table 1 below. The minimum inaforesard. h1b1tory concentratlon 1s given 1n 'y/ml.

TABLE 1 Microorganisms testedSample Names of Compounds Tricho- Trz'cho- Staphyla- Strepto- Diplococcus Salmo- Mycobacte Toxicity phyton pin ton Trzchococcus coccus pneumoniae nella Bacillus rium tuber- LD5Q (mg,/ asterinterphyton pyogenes pyogenes D typhi subtilis culosis var. kg.) mouse oides digitale rubrum aureus 00k Neufield 0*90l-W PCI 219 homim's 209-p Group A Type 1 H 37 Rv 2, 4, 6-triehlorophenyl 0.26 0.25 0. 78 2. 0 0.97 O. 24 250 l. 95 31. 2 {i.p.=500.

iodopropargyl ether. oral 3,000. 2, fi-dichlorophenyliodopro- 0. 48 7. 8 3. 9 1. 95 250 3. 9

pargyl ether. 2, ti-dichloro-i-ethoxy- 8.9 3. 12 3. 12 1. 56 3. 12 1. 56 100 3. 12

methylphenyliodo propargyl ether. P-bromophenyl iodopro- 0. 156 0. 312 0. 312 7. 8 7. 8 3. 9 15. 6

pargyl other. O-iodopropargyloxy 31. 2 250 6.25 250 benzamide. Ientaehlorophenyliodo- 100 50 25 propargyl ether. P-nitrophenyl iodopro- 1. 1. 95 1.95 250 250 250 250 250 ,pargyl ether. P-aeetylaminophenyl 15. 6 0. 97 3. 9 250 62. 5 62. 5 250 62. 5

idopropargyl ether. 2, 4-dichloronaphthyl iodo- 3. 9 62. 5 1. 95 62. 5 0. 97 0. 48 250 15. 6

propargyl ether. 2, 4-dichl0rophenyl iodo- 0. 078 0. 312 0. 156 3. 9 1. 95 0.97 250 0.97 {i.p.=320

propargyl ether. oral 3000. P-dtilphenyliodopropargyl 0. 97 1. 56 6. 25 250 250 62. 5 250 250 ora1 500.

e er.

TABLE 1Continued Microorganisms tested-Sample Names of Compounds Tricho- Tricho- Staphylo- Strepto- Dtplococcus Salmo- Mycobactc- Toxicity phyton phyton Trichococcus coccus pneumoniae nella Bacillus rium tubcr- LDsn (11]g./ asterinterphyton pyogenas pyogenes D11 typhi subtilis culosis var. kg.) mouse aides digitale rubrum aureus Cook Neufield -901-W P01 219 hominis 209-p Group A Type 1 H 37 Rv P-ehloro hen liodo r0- 0. 07s 0. 312 0.156 7.8 3. 9 a. 9 15.6 7.8 12:15?

z g. p {0re1 3000 -0111or02-iodopr0pargy1- 0.078 1.25 0.625 12.5 31.2 125 250 15.6 0ra1 3000 oxy benzamide. P-diehloroacetylamino- 0. 48 0. 39 0. 78 250 7.8 31. 2 250 31. 2 or5l 1000 phenyl iodopropargyl ether. P-propaxgyloxyphenyl 0. 156 1. 0. 625 250 15. 6 7. 8 250 250 iodopropargyl ether. P-iodophenyl iodopro- 0.156 0.625 0.312 7. 8 15. 6 7. 8 250 250 {i.p.=420.

pargyl ether. ora1 3,000. P-fi-hydroxyethoxyphenyl 0. 97 0. 78 0. 78 62. 5 62. 5 125 250 62. 5

iodopropargyl ether. Pentaohlorophenyl bromo- 250 250 50 100 12.5 25 100 50 propargyl ether. P-bromophenyl bremopro- 100 110 50 100 12. 5 12. 5 50 50 pargyl ether. P-brornophenyl ehloro- 250 250 50 100 50 50 100 100 propargyl ether. 2, 4, 5-trieh10ropheny1 100 250 50 250 12. 5 6. 25 250 250 brornopropargyl ether. 2, 4, fi-triohlorophenyl 25 50 25 250 6. 25 6. 25 250 250 250 ehloropropargyl ether. 2-methy1-4, 6-dioh10ro- 1. 56 3. 12 3. 12 1. 56 1. 56 0. 78 250 0. 39 250 phenyl iodopropargyl ether. P-fiuorophenyl iodopro- 0. 1. 56 0. 78 6. 25 6. 25 6. 25 12. 5 6. 25 10-50 pargyl ether. P-chlorophenyl bromo- 6. 25 6. 25 12. 5 250 12. 5 25 250 100 50 propargyl ether. 2, 4-dioh1orophonyl bromo- 3. 12 6. 25 12.5 250 100 6. 25 250 250 10-50 propargyl ether. 2, 4-dieh1oropheny1 chloro- 6. 25 12. 5 25 25 3.12 3.12 250 12. 5 50 propargyl ether. P-carboxyphenyliodo- 0. 39 0. 78 0. 78 25 25 25 100 25 propargyl ether. 2-nitro-4-rnethy1pheny1 0. 19 0.39 0.78 6- 25 6. 25 6. 25 100 6.25

iodopropargyl ether. 3-nitro-4-methy1pheny1 0.19 0. 39 0.78 6. 25 6. 25 6. 25 100 3.12

iodopropargyl ether. P-aeetylphenyl iodopro- 100 100 100 50 25 12.5 50 50 pargyl ether. P-earbomethyoxyphenyl 1. 56 8. 12 3.12 6. 25 6. 25 12.5 100 6. 25

iodopropargyl ether. P-carbomethyoxyphenyl 6. 25 3. 12 12. 5 100 100 12. 5 100 100 bromopropargyl ether. P-eyanophenyl iodopro- 0. 78 1. 56 3.12 6. 25 12. 5 25 100 25 pargyl ether.

For the purpose of companson, the actlvrty of the ha1o- TABLE 2*C0ntinuad propargyl a=ry1 ether compounds of the present lnventron may be compared to the -act1v1ty of the corespondlng non- Names of the fungi tested halogenated propargyl aryl ether compounds whrch are used as the startlng matenal for the process of the present Structural formulae of Trim Tm TN-chm lnventlon. To thls end, the rnmnnum eoncentratlons of com ounds tested pfiylon gghytodn pig ton some compounds lnhrbltory to Trzchophyton mterdzgztale', 5.3555,. m mm Trichophyton asterozdes and Trlchophyton rubruml are tested by the conventronal drlutron method and grven 1n 01 'y/ 1111. 1n Table 2 below. I

. HC COHzO-Q 1, e00

01 TABLE 2 l IC CCHZO 0.5 Names of the fungi tested C1 Stmetural formulae of Tricho- Tn'cho- Trichocompounds tested phyton phyton phyion .interasteroides Tubrum HC E C C 1120 C1 250 digitale C1 HzN C O I HzNC 0 10 C 01120 01 625 156 M25 For thrs table, .1t 15 clear that the rodopropargyl aryl C1 ether compounds of th1s rnven'non exhlbrt consrderably hlgher actlvlty than the correspondmg non-halogenated propargyl aryl ether compounds from which the aforesaid halopropargyl varyl ether compounds started.

In order to illustrate the process of the invention the folowing examples are now shown but the scope of the invention is not limited to them,

Example 1 8.5 grams of para-bromophenyl propargyl ether '(B.P. 8087 C./ 1.5 mm, Hg) are added to an aqueous solution of cupro-ammoniurn complex salt which has been prepared by Warming a mixture of 8.0 grams of cuprous chloride, 20.0 grams of ammonium carbonate and 200 cc. of water to 50 C. The resulting admixture is shake-d vigarously. The cuprous \acetylide deposited is filtered, Washed with water and suspnded in 200 cc. of water. The suspension is added under agitation with a solution of 10.4 grams of iodine and 10.4 grams of potassium iodide in 25 cc, of Water. The mixture is stirred for a period of 1 hour. The precipitation is subsequently filtered, Washed with water and then extracted with ether. After the etheral extract has been dried, the ether is distilled oil. Recrystallisation of the residue from n-hexane gives about 9.8 grams of para broinophenyl iodopropargyl ether, M.P. 70-71 C.

Example 2 5.3 grams of 2,6-dichlorophenyl propargyl ether (M.P. 4546 C.) are added to an aqueous solution of cuproammonium complex salt which has been prepared by Warming a mixture of 5 .5 grams of cuprous chloride, 14.0 grams of ammonium carbonate and 100 cc. of Water to 50 C. The resulting admixture is shaked vigorously. The cuprous acetylide deposited is filtered, Washed with water and suspended in 150 cc. of Water. The resulting suspension is mixed under agitation with a solution of 3.6 grams of iodine and 3.6 grams of potassium iodide in cc. of Water. The mixture is stirred for a period of 1 hour. The precipitation is filtered, Washed with Water and extracted with ether. After the etheral extract has been dried, the solvent is distilled off, Recrystallisation of the residue from n-hexane give-s about 5.0 grams of 2,6-dichlorophenyl iodopropargyl ether, M.P. 49-50 C.

Example 3 4.7 grams of 2,4,5-trichlorophenyl propargyl ether (M.P. 64-65 C.) are added to an aqueous solution of cupro-ammonium complex salt which has been prepared by warming a mixture of 4.0 grams of cuprous chloride, 11.0 grams of ammonium carbonate and 20 cc. of water to 50 C. The resulting admixture is shaked vigorously. The cuprous acetylide deposited is filtered, Washed Wtih water and suspended in 100 cc. of water, and the suspension is mixed under agitation with a solution of 5.0 grams of iodine and 5.0 grams of potassium iodide in cc. of water. The mixture is stirred for a period of 1 hour. The preciptation is filtered, washed with water and extracted with ether. After the drying of the etheral extract, the solvent is distilled off. Recrystalli-sation of the residue from n-hexane gives about 5.6 iodopropargyl ether, M.P. 114-1 15 C.

Example 4 6.8 grams of 2,4,6-trichlorophenyl propargyl ether are added to 70 cc. of methanol and this solution is then mixed with a solution of 3.5 grams of sodium hydroxide in 10 cc. of water. The resulting mixture is cooled down in an ice-water bath and added under agitation with 7.5 grams of iodine in small portions. The temperature of the mixture is kept at 5 -l0 C. After the whole amount of iodine has been added, the solution is stirred for further one hour. The crystal deposited is then filtered, Washed with Water and dried. Recrystallisation from isopropyl alcohol gives about 8.0 grams of 2,4,5-trichlorophenyl iodopropargyl ether.

grams of 2,4,5-trichlorophenyl 0 Example 5 4.0 grams of pentachlorophenyl propargyl ether are dissolved in carbon tetrachloride and this solution is mixed with a solution of 2.1 grams of bromine in 2.0 cc. of carbon tetrachloride in small portions With irradiation of sunlight. After the color of bromine has been vanished, the carbon tetrachloride is distilled oif. Recrystallisation of the residue from isopropyl alcohol gives about 3.3 grams of pentachlorophenyl 2,3-dibromoally1 ether, M.P. 120-121 C.

16.5 grams of pentachlorophenyl 2,3-dibromoally1 ether so obtained are added to a solution of sodium alcoholoate which has been prepared by dissolving 0.82. gram of metallic sodium in 50 cc. of ethanol. The mixture is boiled under reflux for 1 hour and then distilled so as to remove the ethanol. Addition of cc. of water to the mixture causes the deposition of crystal which is then filtered and dried. Recrystallisation from isopropyl alcohol gives about 5.1 grams of pentachlorophenyl bromopropargyl ether, M.P. 127-129 C.

Example 6 para-nitrophenyl propargyl ether (M.P. 112112.5 C.) are dissolved in 100 cc. of methanol and the resulting solution is then mixed with a solution of 11 grams of potassium hydroxide in 25 cc. of water. The mixture is cooled down in an ice-Water bath and added under agitation with 19.3 grams of iodine in small portions While the temperature of the mixture is kept at 5-10 C. After the Whole amount of iodine has been added, agitation is continued for further one hour. Addition of 200 cc. of water causes the deposition of crystal which is then filtered, Washed with water and dried. Recrystallisation from methanol gives about 16.0 grams of para-nitrophenyl iodopropargyl ether, M.P. 1 84-185 C.

Example 7 9.0 grams of para-acetylaminophenyl propargyl ether, M.P. 114-11 6 C. are dissolved in 100 cc. of methanol and the resulting solution is mixed with a solution of 7.0 grams of potassium hydroxide in 15 cc. of water. The mixture is then cooled down in an ice-Water bath and added under agitation with 18 grams of iodine in small portions at a temperature of 5-1'0 C., so that the halogenation reaction takes place. After the whole amount of iodine has been added, agitation is continued for further one hour. Addition of 200 cc. of Water causes the deposition of crystal which is then filtered, washed with water and dried. Subsequent recrystallisation from isopropyl alcohol gives about 9.5 grams of para-acetylaminophenyl iodopropargyl ether, M.P. 138-139 C.

Example 8 5.3 grams of ortho-propargyl hydroxybenzamide, M.P. 147.5-148 C. and 3.7 grams of potassium hydroxide are dissolved in 40 cc. of water. The resulting solution is cooled down in an ice-Water bath and added under agitation with 7.7 grams of iodine in smal portions while the temperature of the admixture is kept at 5-10 C. After one hours agitation, the crystal deposited is filtered, washed with water and dried. Subsequent recrystallisation from methanol gives about 5.5 grams of orthor-iodopropargyl hydroxybenzamide, M.P. 173174 C.

Example 9 21.4 grams of Z-methyl-4,6-dichlorophenyl propargyl ether, M.P. 76-77" C. are dissolved in 300 cc. of methanol and the resulting solution is mixed with a solution of 8.8 grams of sodium hydroxide in 20 cc. of water. The mixture is cooled down in an ice-water bath and added with 25.4 grams of iodine under agitation in the same conditions as in Example 6. Subsequent similar treatment followed by recrystallisation from isopropyl alcohol gives about 25.0 grams of 2-methyl-4,6-dichlorophenyl iodopropargyl ether, M.P. 91-915 C.

13.5 grams of 7. Example 10 4.5 grams of 2,4-dichloronaphthy1 propargyl ether, M.P. 97-98" C. are dissolved in 50 cc. of methanol and the resulting solution is mixed with a solution of 3.0 grams of potassium hydroxide in 10 cc. of water. The mixture is then added with 7.0 grams of iodine under the same conditions as in Example 6. Addition of 100 cc. of Water causes the deposition of crystal which is then filtered, washed with water and dried. Recrystallisation from methanol gives 5.5 grams of 2,4-dichloronaphthyl iodopropargyl ether, M.P. 109-110 C.

Example 11 20 grams of 2,4-dichlorophenyl propargyl ether, M.P. 49-50 C. are dissolved in 200 cc. of methanol and the resulting solution is mixed with a solution of 8.8 grams of sodium hydroxide in 20 cc. of water. The mixture is cooled down in an ice-Water bath and dropwise added with 16.0 grams of brominein small portions and under agitation while the temperature of the mixture is kept at -10 C. After the whole amount of bromine has been added, the agitation is continued for further one hour. Addition of 300 cc. of water causes the deposition of crystal which is then filtered, washed with water and then dried. Subsequent recrystallisation from methanol gives about 23.0 grams of 2,4-dichlor-ophenyl bromopropargyl ether, MJP. 7676.5 C.

Example 12 21.1 grams of p-bromophenyl propargyl ether are dissolved in 200 cc. of methanol and the resulting solution is added with a solution of 8.8 grams of sodium hydroxide in 15 cc. of water. The mixture is cooled down in an icewater bath and passed therethrough with chlorine gas under agitation and at a temperature of l5 C. Methanol is then distilled oil under reduced pressure. Addition of 200 cc. of water to the residue causes the deposition of an oily substance which is then extracted with ether. The etheral extract is dried and then distilled so as to remove the ether. Petroleum ether is added to the remaining oily substance and the crystal deposited is recrystallised from ether. Yield is about 13.0 grams of pbromophenyl chloropropargyl ether, M.P. 28-29 C.

Example 13 20.0 grams of 2,4-dichlorophenyl propargyl ether is dissolved in 200 cc. of methanol and the resulting solution is mixed with a solution of 8.8 grams of sodium hydroxide in 15 cc. of water. The resultant mixture is cooled down in an ice-water bath and passed therethrough with chlorine gas under agitation while the temperature of the mixture is kept at 10-15 C. Methanol is distilled off under reduced pressure and 200 cc. of water are added to the residue. An oily substance deposited is extracted with ether and the ethreal extract so obtained is dried. Distillation off of the ether gives an oily residue which is then distilled under a reduced pressure of 0.01 mm. Hg to recover an oily fraction which can be distilled out at the bath temperatures between 120 C. and 130 C. Yield is about 15.0 grams of 2,4-dichlorophenyl chloropropargyl ether.

Example 14 10.0 grams of 2,4,5-trichlorophenyl propargyl ether are dissolved in 150 cc. of ethanol and the resulting solution is mixed with a solution of 4.8 grams of potassium hydroxide in 10 cc. of water. The resultant mixture is cooled down in an ice-water bath and passed therethrough with chlorine gas under agitation while the temperature of the reaction mixture is kept at 5 C.10 C. Subsequent addition of 300 cc. of water causes the deposition of crystal which is then filtered, washed with water and dried. Recrystallisation from isopropyl alcohol gives about 8.1 grams of 2,4,5-trichlorophenyl chloropropargyl ether, M.P. 6869 C.

8 Example 15 15.2 grams of pentachlorophenyl propargyl ether, M.P. 139-140 C. are dissolved in 300 cc. of methanol and the resulting solution is added with a solution of 4.4 grams of sodium hydroxide in 10 cc. of water. The admixture is cooled down in an ice-water bath and then added under agitation with 12.7 grams of iodine in small portions while the temperature of the mixture is kept at 510 C. After the whole amount of iodine has been added, the agitation is continued for further one hour. Subsequent addition of 500 cc. of water causes the deposition of crystal which is filtered, Washed with water and dried. Recrystallisation from isopropyl alcohol gives about 17.0 grams of pentachlorophenyl iodopropargyl ether, M.P. 140.5 C.

Example 16 20.0 grams of 2,4-dichlorophenyl propargyl ether, M.P. 4950 C. are dissolved in 200 cc. of methanol and the resulting solution is mixed with a solution of 8.8 grams of sodium hydroxide in 20 cc. of water. The admixture is cooled in an ice-water bath and then added under agitation with 25.4 grams of iodine in small portions while the temperature of the mixture is kept at 510 C. After the whole amount of iodine has been added, the agitation is continued for further one hour. Subsequent addition of 300 cc. of Water causes the deposition of crystal which is then filtered, washed with water and dried. Recrystallisation from isopropyl alcohol gives about 23 grams of 2,4-dichlorophenyl iodopropargyl ether, M.P. 9394 C.

Example 17 67 grams of p-chlorophenyl propargyl ether, HP. 62- 64 C. at 0.15 mm. Hg are dissolved in 500 cc. of methanol and the resulting solution is mixed with a solution of 36 grams of sodium hydroxide in 50 cc. of water. The admixture is cooled in an ice-water bath and then added under agitation with 103.0 grams of iodine in small portions at the temperature of 5l0 C. After the Whole amount of iodine has been added, the agitation is continue-d for further one hour. Subsequent addition of 500 cc. of water causes the deposition of crystal which is filtered, washed with water and dried. Recrystallisation from normal hexane gives about 92.5 grams of p-chlorophenyl iodopropargyl ether, M.P. 52-53 C.

Example 18 A solution of 18.6 grams of p-iodophenyl propargyl ether, M.P. 4244 C. in cc. of methanol is mixed with a solution of 11.5 grams of sodium hydroxide in 20 cc. of water. The resulting admixture is cooled in an ice-Water bath and then added under agitation with 18.3 grams of iodine. Agitation is continued for further 2 hours. Addition of 200 cc. of Water causes the precipitation of a crude product which is then filtered, washed with water and dried. Recrystallisation from normal hexane gives about 18.0 grams of p-iodophenyl iodopropargyl ether, M.P. 98-99 C.

Example 19 A solution of 3.2 grams of p-fluorophenyl propargyl ether in 100 cc. of methanol is mixed with a solution of 3.2 grams of sodium hydroxide in 10 cc. of water. The resulting admixture is cooled in an ice-water bath and then added with 5.4 grams of iodine under agitation. After 2 hours, the reaction mixture is distilled under reduced pressure to remove the methanol. The residue is extracted with ether, the ethereal extract is dried and the solvent is distilled oil therefrom. The remaining liquid is distilled under a reduced pressure of 0.2 mm. Hg to yield about 3.1 grams of p-fluorophenyl iodopropargyl ether which is distilled out at the temperature of 101-102 C.

Example 20 with a solution of 6.0 grams of sodium hydroxide in 10 cc. of water. The resulting admixture is cooled in an ice- Water bath and then added with 18.5 grams of iodine under agitation. The agitation is continued for further one hour, and subsequent addition of 100 cc. of Water causes the precipitation of a crude product which is filtered, washed with water and dried. Recrystallisation from methanol gives about 6.4 grams of p-propargyloxyphenyl iodopropargyl ether, M.P. 121-122 C.

Example 21 A solution of 1.92 grams of para-fi-hydroxyethoxyphenyl propargyl ether, M.P. 74-75" C. in 20 cc. of methanol is mixed with a solution of 0.9 gram of sodium hydroxide in 3 cc. of water. The resultant admixture is cooled in an ice-water bath and then added with 2.55 grams of iodine under agitation. After 1 hour, a crude product precipitated, is filtered, washed with water and dried. Recrystallisation from isopropyl alcohol gives about 2.85 grams of para-fi-hydroxyethoxyphenyl iodopropargyl ether, M.P. 73.574.5 C.

Example 22 A solution of 13.5 grams of p-diphenyl propargyl ether, M.P. 7678 C. in 130 cc. of methanol is mixed with a solution of 16 grams of sodium hydroxide in 20 cc. of water. The admixture is cooled in an ice-water bath and then added with 16.5 grams of iodine under agitation. After 1 hour, the crystal deposited is filtered, washed with Water and dried. Recrystallisation from isopropyl alcohol gives about 10.0 grams of p-diphenyl iodopropargyl ether, M.P. 124-125 C.

Example 23 A solution of 4.5 grams of 2,6-dibromo-4-ethoxymethylphenyl propargyl ether, M.P. 68-70 C. in 40 cc. of methanol is mixed with a solution of 5.6 grams of sodium hydroxide in 10 cc. of water. The resulting admixture is cooled in an ice-water bath and then added with 3.6 grams of iodine under agitation. The crystal deposited is filtered, washed with water and dried. Recrystallisation from normal hexane gives about 3.0 grams of 2,6-dibromo-4-ethoxymethylphenyl iodopropargyl ether, M.P. 67.5-68 C.

Example 24 A solution of 6.9 grams of 3-nitro-4-methylphenyl propargyl ether, M.P. 4546 C. in 150 cc. of methanol is mixed with a solution of 3.3 grams of sodium hydroxide in cc. of water. The resultant admixture is cooled in an ice-water bath and then added with 9.2 grams of iodine under agitation. The agitation is continued for further 2 hours, and subsequent addition of 200 cc. of water causes the precipitation of a crude product which is then filtered, Washed with water and dried. Recrystallisation from n-hexane gives about 10.0 grams of 3-nitro-4- methylphenyl iodopropargyl ether, M.P. 102.5103.5 C. Example 26 A solution of 5.0 grams of p-acetylphenyl propargyl ether, M.P. 76.577.5 C. in 100 cc. of methanol is mixed with a solution of 2.5 grams of sodium hydroxide in cc.

of water. The resulting admixture is cooled in an ice-water bath and then added with 7.3 grams of iodine under agitation. Addition of cc. of water subsequent to one hours agitation causes the deposition of crystal which is then filtered, washed with water and dried. Recrystallisation from methanol gives about 3.5 grams of p-acetylphenyl iodopropargyl ether, M.P. 117-118 C.

Example 27 A solution of 1.27 grams of p-dichloroacetylaminophenyl propargyl ether, M.P. 124124.5 C. in 20 cc. of methanol is mixed with a solution of 0.5 gram of sodium hydroxide in 2 cc. of water. The resulting admixture is cooled in an ice-water bath and then added with 1.25 grams of iodine under agitation. The agitation is continued for further one hour, and subsequent addition of 50 cc. of water causes the deposition of crystal which is then filtered, washed with water and dried. Recrystallisation from isopropyl alcohol gives about 1.3 grams of pdichloroacetylaminophenyl iodopropargyl ether, M.P. 148.5149 C.

Example 28 A solution of 10.5 grams of 5-chloro-2-propargyloxy benzamide, M.P. 134.5135.5 C. is 150 cc. of methanol is mixed with a solution of 4.4 grams of sodium hydroxide in 10 cc. of water. The admixture is cooled and then added with 12.7 grams of iodine under agitation at the temperature of approximately 5 C. After 1 hours agitation, the crystal deposited is filtered, Washed With methanol and subsequently with water and then dried. Recrystallisation from methanol gives about 13.3 grams of 5-chloro-2iodopropargyloxy benzarnide, M.P. 169.5- 170.5 C.

Example 29 8.8 grams of pcarboxyphenyl propargyl ether with decomposition point of 210-211" C., are added with 100 cc. of water and 6.6 grams of sodium hydroxide. The resulting admixture is cooled in an ice-water bath and then added further with 12.7 grams of iodine under agitation. After one hours agitation, the mixture is made acidic by addition of hydrochloric acid. The precipitation deposited is filtered, washed with water and dried. Recrystallisation from methanol gives about 13.7 grams of p-carboxyphenyl iodopropargyl ether which decomposed at 220 C.

Example 30 A solution of 51 grams of p-chlorophenyl propargyl ether in 300 cc. of methanol is mixed with a solution of 28 grams of sodium hydroxide in 40 cc. of water. The resulting admixture is cooled in an ice-water bath and then added under agitation with 49.0 grams of bromine in small portions While the temperature of the mixture is kept at 5-10 C. After the whole amount of bromine has been added, agitation is continued for further 1 hour. Subsequent addition of 500 cc. of Water causes the deposition of crystal which is then filtered, Washed with Water and dried. Recrystallisation from petroleum ether gives about 38.7 grams of p-chlorophenyl bromopropargyl ether, M.P. 50.551.5 C.

Example 31 A solution of 13.7 grams of p-bromophenyl propargyl ether, B.P. 80-87" C. at 1.5 mm. Hg in 200 cc. of methanol is mixed with a solution of 12 grams of sodium hydroxide in 15 cc. of water. The resulting admixture is cooled in an ice-water bath and then dropwise added under agitation with 10.4 grams of bromine while the temperature of the mixture is kept at 5-10 C. After the whole amount of bromine has been added, the agitation is continued for further 1 hour. Methanol is distilled off under a reduced pressure. After addition of 200 cc. of water, the mixture is extracted with ether and the etheral extract is Washed with water, dried and then distilled to remove the solvent. Recrystallisation of the residue from n-hexane gives about 5.5 grams of p-bromophenyl bromopropargyl ether, M.P. 5859.5 C.

11 Example 32 A solution of 10.0 grams of 2,4,5-trichlorophenyl propargyl ether, M.P. 64-65 in 100 cc. of methanol is mixed with a solution of 3.4 grams of sodium hydroxide in 10 cc. of water. The resulting admixture is cooled in an icewater bath and then dropwise added with 6.7 grams of bromine under agitation while the temperature of the mixture is kept at about C. After the whole amount of bromine has been added, the agitation is containued for further one hour. Subsequent addition of 200 cc. of water causes the deposition of crystal which is then filtered, Washed with water and dried. Recrystallisation from isopropyl alcohol gives about 6.5 grams of 2,4,5-trichlorophenyl bromopropargyl ether, M.P. 102.5-103.5 C.

Example 33 A suspension of 9.0 grams of p-cyanophenyl propargyl ether, M.P. 112-113 C. in 100 cc. of ethanol is mixed with an aqueous solution of grams of potassium hydroxide in 10 cc. of water. The resulting mixture is added with 16.0 grams of iodine in small portions under agitation while being cooled in an ice-water bath. After the whole amount of iodine has been added, the agitation is continued for further 3 hours. The reaction mixture is then added with 300 cc. of water, and the precipitation deposited is filtered, washed with water and dried. Recrystallisation from ethanol gives about 12.0 grams of pcyanophenyl iodopropargyl ether, M.P. 161-l62 C.

Example 34 A solution of 3.35 grams of sodium hydroxide in 10 cc. of water is mixed with 100 cc. of methanol, and the mixture is cooled in an ice-water bath under agitation to which are then added 7.25 grams of p-carbomethoxyphenyl propargyl ether. The resulting admixture is subsequently added with 9.65 grams of diodine in small portions while the temperature of the mixture is kept at 5-10 C. After the whole amount of iodine has been added, the agitation is further continued for 1 hour. Addition of 300 cc. of water causes the deposition of the precipitation which is then filtered, washed with Water and dried. Recrystallisation from methanol gives about 9.65 grams of p-carbomethoxyphenyl iodopropargyl ether, M.P. 97-98 C.

Example 35 A solution of 3.3 grams of sodium hydroxide in 10 cc. of water is mixed with 100 cc. of methanol. The mixture is cooled in an ice-water bath under agitation to which are then added 7.1 grams of p-carbomethoxyphenyl propargyl ether and subsequently 7.3 grams of bromine dropwise in small portions while the temperature of the mixture is kept at 5-10 C. After the whole amount of bromine has been added, the agitation is continued further for 30 minutes. Subsequent addition of 300 cc. of water causes the deposition of the precipitation which is then filtered, washed with water and dried. Recrystallisation from methanol gives about 8.5 grams of p-carbomethoxyphenyl bromopropargyl ether, M.P. 77.5-78.5" C.

What we claim is:

1. Iodopropargyl aryl ether compounds represented by the general formula:

wherein Ar stands for substituted phenyl and naphthyl groups which carry on the aromatic nucleus substituents selected from the group consisting of halogen, nitro, cyano, lower alkyl, lower alkoxy, lower alkynyloxy, hydroxy lower alkoxy, phenyl and acetyl radicals.

. 2,4,5-trichlorophenyl iodopropargyl ether.

. 2,6-dichlorophenyl iodopropargyl ether.

. p-Bromophenyl iodopropargyl ether.

. p-Nitrophenyl iodopropargyl ether.

. 2,4-dichlorophenyl iodopropargyl ether.

. p-Chlorophenyl iodopropargyl ether.

p-Iodophenyl iodopropargyl ether.

2-methyl-4,6-dichlor0phenyl iodopropargyl ether. 10. p-Fluorophenyl iodopropargyl ether.

11. 2-nitro-4-methylphenyl iodopropargyl ether.

12. 3-nitro-4-methylphenyl iodopropargyl ether.

13. p-Cyanophenyl iodopropargyl ether.

References Cited UNITED STATES PATENTS 10/1958 Barthel 167-30 2/1959 Haynes et al 167'30 1/1960 Muller et al 260562 6/ 1960 Cameron.

7/1961 Rosen 2606l2 OTHER REFERENCES Coates: Organo-Metallic Compounds, 1960, pp. 353- 354.

CHARLES B. PARKER, Primary Examiner.

IRVING MARCUS, Examiner.

DALE R. MAHANAND, DOLPH H. TORRENCE,

Assistant Examiners. 

1. IODOPROPARGYL ARYL ETHER COMPOUNDS REPRESENTED BY THE GENERAL FORMULA: 